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Thursday, November 21, 2013

Burning sensation heralds death from paraquat poisoning


I came upon this deliciously morbid tidbit of information the other day and couldn't resist posting about it: in one type of herbicide poisoning, impending death is heralded by the sensation of being burned alive. A bunch of researchers from Sri Lanka found this out after doing a study in 3 hospitals. I'm talking about paraquat poisoning.



Image courtesy of: 9comeback / Free Digital Photos (www.freedigitalphotos.net)


Paraquat is the trade name for N,N′-dimethyl-4,4′-bipyridinium dichloride, one of the most widely used herbicides in the world. Quick-acting and non-selective, it kills green plants on contact. It is also toxic to plants and animals

According to Wikipedia, a large majority (93%) of fatalities from paraquat poisoning are cases where the poison was ingested intentionally, i.e., suicides. In Third World countries, paraquat is a major suicide agent. For instance, in Samoa from 1979–2001, 70% of suicides were by paraquat poisoning. In southern Trinidad, particularly in Penal, Debe from 1996–1997, 76% of suicides were by paraquat, 96% of which involve the over-consumption of alcohol such as rum. Fashion celebrity Isabella Blow, depressed because of a cancer diagnosis, committed suicide using paraquat in 2007.

Paraquat is such a widely used suicide agent in Third World countries because of its widespread availability, low toxic dose (10 ml or 2 teaspoons is enough to kill) and relative low cost. There are campaigns to control or even ban paraquat outright, and there are moves to restrict its availability by requiring user education and the locking up of paraquat stores.

Ingestion of paraquat leads to the generation of free oxygen radicals. These free oxygen radicals cause lipid peroxidation, damaging cell membranes and leading to cell death. Paraquat generates such a huge amount of free radicals that free radical scavengers such as glutathione are rapidly overwhelmed. The case fatality rate of paraquat poisoning is high - over 65% in Sri Lanka, for example.

Paraquat is actively taken up into lung cells and renal tubular cells. Thus, in less severe poisonings, kidney and lung damage as well as direct gastrointestinal effects are the main clinical manifestations. In poisonings that are not fatal within days, pulmonary fibrosis can still develop and slowly kill the patient. Increasing concentrations of inhaled oxygen increase pulmonary toxicity presumably by enhancing oxygen radical generation.



Paraquat molecule. Image from: Wikipedia


And now for the interesting part - the 'peripheral burning sensation' which signals that a patient with paraquat poisoning is likely to die.

While conducting two studies on paraquat toxicity in Sri Lanka, medical and research staff noted that patients who complained of a burning sensation of the skin of trunk and limbs (described as if their skin was on fire) seemed more likely to die. This symptom was distinctly different from the burning stomach pain commonly experienced by patients who have ingested paraquat. It was termed ‘peripheral burning pain’ and a study was initiated to see if it can be used to predict the clinical outcome of paraquat poisoning.

The study was conducted from January 2006 to June 2008 on 175 patients who had deliberately ingested paraquat. There were 84 deaths, giving an overall case fatality rate of 48%. The burning sensation was reported in 84 patients (48%), beginning at a median of 1 day (range 1-3 days) after ingestion. Of the patients who had burning, 61 died (case fatality rate nearly 73%), whereas of the 91 patients who had no peripheral burning, 23 died (CFR just over 25%). Thus, the presence of peripheral burning sensation was associated with a significantly higher risk of death. Patients who complained of peripheral burning died at a median of 36 hours following ingestion while those who had no peripheral burning died at a median of 50.5 hours. Moreover, the median admission plasma paraquat concentration in patients with peripheral burning (2.67 μg/mL) was significantly higher than in the patients with no peripheral burning (0.022 μg/mL).

The researchers conclude that the presence of a burning sensation is associated with high plasma paraquat concentrations and is strongly predictive of death. The mechanism of this symptom is not clear. It is possible that the peripheral burning sensation is due to a primary effect of paraquat on peripheral pain receptors; however, it might also be a result of paraquat-induced oxidative stress.

And why is all this so important? Plasma paraquat concentrations are a reliable marker of poor prognosis; however, laboratory testing is not routinely available in many Third World hospitals, where resources are scarce. Thus, it's useful to know that the 'peripheral burning' symptom indicates a high plasma concentration of poison and a probable death.


Literature:

Gawarammana IB, Dawson AH (2010) Peripheral burning sensation: a novel clinical marker of poor prognosis and higher plasma-paraquat concentrations in paraquat poisoning. Clin Toxicol (Phila). 48(4):347-9. doi: 10.3109/15563651003641794.

Wikipedia: Paraquat




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